Molecularly defined circuits for cardiovascular and cardiopulmonary control

Area of Science:

• Neuroscience
• Cardiovascular Biology
• Autonomic Nervous System Research

Background:

• The autonomic nervous system, comprising sympathetic and parasympathetic branches, regulates internal organ functions.
• The specific molecular and functional diversity of neurons and circuits within these systems, particularly for cardiac control, is not fully understood.

Purpose of the Study:

• To dissect the cardiac parasympathetic control circuit in mice.
• To identify and characterize distinct neuronal subtypes within the brainstem nucleus ambiguus (Amb) that innervate the heart.

Main Methods:

• Retrograde neuronal tracing
• Single-cell RNA sequencing
• Optogenetics
• Physiological experiments

Main Results:

• Two distinct subtypes of cardiac-innervating neurons were identified in the nucleus ambiguus: ambiguus cardiovascular (ACV) and ambiguus cardiopulmonary (ACP) neurons.
• ACV neurons (approx. 35 per Amb) form the classical cardiac parasympathetic circuit, regulating heart rate and atrioventricular node conduction via the baroreceptor reflex.
• ACP neurons (approx. 15 per Amb) innervate both cardiac and lung parasympathetic ganglion neurons, mediating the dive reflex (bradycardia and bronchoconstriction).

Conclusions:

• Parasympathetic control of the heart involves two parallel circuits: one for cardiac-specific function (ACV) and another coordinating cardiac and pulmonary function (ACP).
• This discovery offers new insights into the neural control of cardiorespiratory systems.
• Findings have implications for treating cardiac and pulmonary diseases and understanding organ coordination circuits.